合成路线:Cariporide has been obtained by two similar ways:1) The oxidation of 4-isopropylbenzaldehyde (I) with sodium perborate in hot acetic acid gives 4-isopropylbenzoic acid (II),which is sulfonated with hot chlorosufonic acid yielding 3-(chlorosulfonyl)-4-isopropylbenzoic acid (III).The reduction of (III) with sodium sulfite in hot NaOH solution affords 4-isopropyl-3-sulfinobenzoic acid (IV),which is alkylated with methyl bromide and NaOH in DMF giving 4-isopropyl-3-(methylsulfonyl)benzoic acid (V).The reaction of (V) with SOCl2 in refluxing toluene yields 4-isopropyl-3-(methylsulfonyl)benzoyl chloride (VI),which is finally condensed with guanidine (VII) in DMF.2) The iodination of 4-isopropylbenzoic acid (II) with iodine chloride or N-iodosuccinimide (NIS) gives 3-iodo-4-isopropylbenzoic acid (VIII),which is treated first with SOCl2 to afford the corresponding acyl chloride (IX),and then with methanol yielding 4-iodo-4-isopropylbenzoic methyl ester (X).The reaction of (X) with sodium methylsulfite (XI) gives 4-isopropyl-3-(methylsulfonyl)benzoic acid methyl ester (XII),which is finally treated with guanidine (VII) in refluxing THF.
参考文献标题:Diacyl substd.guanidines,process for their preparation,their use as medicament or diagnostic reagent and medicament containing them
文献作者:Kleemann,H.-W.; Lang,H.-J.; Weichert,A.; Crause,P.; Scholz,W.; Albus,U.; Schwark,J.-R.(Aventis SA)
参考来源:CA 2130703; DE 4328352; EP 0640587; JP 1995082234
合成路线:Cariporide has been obtained by two similar ways:1) The oxidation of 4-isopropylbenzaldehyde (I) with sodium perborate in hot acetic acid gives 4-isopropylbenzoic acid (II),which is sulfonated with hot chlorosufonic acid yielding 3-(chlorosulfonyl)-4-isopropylbenzoic acid (III).The reduction of (III) with sodium sulfite in hot NaOH solution affords 4-isopropyl-3-sulfinobenzoic acid (IV),which is alkylated with methyl bromide and NaOH in DMF giving 4-isopropyl-3-(methylsulfonyl)benzoic acid (V).The reaction of (V) with SOCl2 in refluxing toluene yields 4-isopropyl-3-(methylsulfonyl)benzoyl chloride (VI),which is finally condensed with guanidine (VII) in DMF.2) The iodination of 4-isopropylbenzoic acid (II) with iodine chloride or N-iodosuccinimide (NIS) gives 3-iodo-4-isopropylbenzoic acid (VIII),which is treated first with SOCl2 to afford the corresponding acyl chloride (IX),and then with methanol yielding 4-iodo-4-isopropylbenzoic methyl ester (X).The reaction of (X) with sodium methylsulfite (XI) gives 4-isopropyl-3-(methylsulfonyl)benzoic acid methyl ester (XII),which is finally treated with guanidine (VII) in refluxing THF.
参考文献标题:Substd.benzoic acid esters,process for their preparation and their use for the synthesis of inhibitors of the cellular Na+/H+-exchange
文献作者:Kleemann,H.-W.(Aventis SA)
参考来源:DE 4428480
合成路线:Cariporide has been obtained by two similar ways:1) The oxidation of 4-isopropylbenzaldehyde (I) with sodium perborate in hot acetic acid gives 4-isopropylbenzoic acid (II),which is sulfonated with hot chlorosufonic acid yielding 3-(chlorosulfonyl)-4-isopropylbenzoic acid (III).The reduction of (III) with sodium sulfite in hot NaOH solution affords 4-isopropyl-3-sulfinobenzoic acid (IV),which is alkylated with methyl bromide and NaOH in DMF giving 4-isopropyl-3-(methylsulfonyl)benzoic acid (V).The reaction of (V) with SOCl2 in refluxing toluene yields 4-isopropyl-3-(methylsulfonyl)benzoyl chloride (VI),which is finally condensed with guanidine (VII) in DMF.2) The iodination of 4-isopropylbenzoic acid (II) with iodine chloride or N-iodosuccinimide (NIS) gives 3-iodo-4-isopropylbenzoic acid (VIII),which is treated first with SOCl2 to afford the corresponding acyl chloride (IX),and then with methanol yielding 4-iodo-4-isopropylbenzoic methyl ester (X).The reaction of (X) with sodium methylsulfite (XI) gives 4-isopropyl-3-(methylsulfonyl)benzoic acid methyl ester (XII),which is finally treated with guanidine (VII) in refluxing THF.
参考文献标题:Cariporide Mesylate
文献作者:Graul,A.; Prous,J.; Castar,J.
参考来源:Drugs Fut 1997,22(11),1197
合成路线:Two new related ways for the synthesis of cariporide mesylate have been reported:1) The reaction of 4-isopropylbenzoic acid (I) with chlorosulfonic acid gives 3-(chlorosulfonyl)-4-isopropylbenzoic acid (II),which is reduced wth sodium sulfite/NaOH to the sorresponding sulfinic acid (III).The methylation of (III) with methyl iodide/NaOH in dimethylacetamide affords 4-isopropyl-3-(methanesulfonyl)benzoic acid methyl ester (IV),which is finally condensed with gunidine (V).2) The hydrolysis of benzoate (IV) with NaOH in methanol/water gives the corresponding free acid (VI),which is then condensed with guanidine (V) by means of dicyclohexylcarbodiimide (DCC) in THF.3) Benzoic ester (IV) can also be obtained by alkylation of 4-bromo-3-(methanesulfonyl)benzoic acid methyl ester with isopropylmagnesium chloride by means of CuI,ZnCl2 and a PdCl2 catalyst in THF.
参考文献标题:Synthesis of the highly selective Na+/H+ exchange inhibitors cariporide mesylate and (3-methanesulfonyl-4-piperidino-benzoyl)guanidine methanesulfonate
文献作者:Lang,H.J.; Scholz,W.; Faber,S.; Weichert,A.; Jansen,H.W.
参考来源:Arzneim-Forsch Drug Res 1997,47(11),1204
产品链接: CAS No. 159138-81-5›› 产品链接: CAS No.159138-80-4››